The article of Hooshmand et al entitled “Complex Regional Pain Syndrome (Reflex Sympathetic Dystrophy Syndrome and Therapy—a Review of 824 Patients” in Pain Digest, Springer—Verlay, New York Inc. 1999 discusses the neuropathic pain with neurovascular dysfunction in patients with complex regional pain syndrome (CRPS) which includes diabetic neuropathy, nutritional neuropathy, fibromyalgia, and the like which involves restriction of blood flow and the reduction of nerve condition velocities.
Fibromyalgia is a disease characterized by pain in the lower extremities and in some cases an autoimmune disease wherein blood circulation is restricted and the nerve endings are affected.
Diabetic neuropathy occupies an important place as one of three major complications of diabetes along with retinopathy and nephropathy.
Diabetic neuropathy is currently categorized into three groups comprising mononeuropathy, symmetrical peripheral polyneuropathy and autonomic neuropathy (Williams Text Book of Endocrinology, 8th Edition, p 1301, Harrison's Principles of Internal Medicine, 12th edition, p 1754).
Mononeuropathy is a focal or multifocal mononeural disorder which appears as lesions of the cerebral nerve or affects soma and/or extremities. Its major symptom emerges as dyskinesia in many cases. It is known to develop more often in elder patients.
Symmetrical peripheral polyneuropathy is the most frequent form of diabetic neuropathy. It generally makes slow progress, so that its patients tend to become aware of the symptoms only after it has reached an advanced stage. The initial symptoms are often a reduced Achilles reflex parasthesis and a decline or absence of vibratory sensibility. Urtication represented as a smarting feeling and then numbness on both feet follow.
With autonomic neuropathy, patients show representative symptoms for autonomic disorder, such as orthostatic hypotension, cardiac rate alteration, dyshidrosis, atony of esophagus or gastric atony, diabetic diarrhea, impotence and others.
As mechanisms for development of these symptoms, metabolic hypothesis and vascular/ischemic hypothesis have been implied. For the former hypothesis, hypergasia of polyol metabolic pathway, a pathway where sorbitol and fructose are produced from glucose provided due to hyperglycemia is considered to be a major contributing factor. Another theory involving a reduced content of myoinositol is related to peripheral nerve disorder. In the latter hypothesis, neuro-microvascular occlusion and/or destruction of blood-nerve barrier are thought to be related to the nerve disorders.
As methods of treatment of diabetic neuropathy, it has been reported that some trial treatments have been conducted during the 1970s and 1980s based upon the hypothesis that abnormality of metabolic factors is viewed as a cause, Greene D A, DeJesus P V Jr., et al. (Effects of insulin and dietary myoinositol on impaired peripheral motor nerve conduction velocity in acute streptozatocin diabetes, J. Clin. Invest., 1975, 55, 6, 1326-36) and Yagihashi S., Nishihira M., et al (Morphometric analysis of the peripheral nerve lesions in experimental diabetes rats, Tohoku J. Exp. Med., 129, 2, 139-49, 1979). These confirmed that peripheral nerve fibers of model rats for diabetic neuropathy were morphologically impaired and NCV was reduced. In addition to that, they reported that when insulin was administered to the rats, improvements in NCV could be observed, thus finding that control over blood glucose level led to improvements in NCV.
Accordingly, current methods of treatment for diabetic neuropathy, dietary therapy and administration of insulin, both mainly proposing to control blood glucose level, administration of aldose reductase inhibitors and aminoguadanine, both mainly proposing to improve abnormal glucose metabolism, administration of troglitazone, and administration of agents for limb ischemia mainly proposing to improve blood flow, have been conducted.
In any treatments, improvement of nerve conduction velocity was not always sufficient when a single drug was used, and methods of treatment by combined use of different therapeutic agents which have different functions have yet to be established. Accordingly, combined drug therapies for diabetic neuropathy aiming at recovering once reduced nerve conduction velocity, have not yet been confirmed.
Toxic neuropathy is similar in symptoms as diabetic neuropathy in that nerve fibers are affected and there is a resultant leg numbness or pricking in the feet.
U.S. Pat. No. 5,981,594 to Okanoto et al discloses the use of a prostaglandin I derivative together with an anti-diabetic agent to hypofunction motor and sensory nerves. However, such treatment has side effects because the prostaglandins are not localized at the sites of the pain.
Because diabetes is a systematic disease affecting many parts of the body, ideal case management requires a team approach. This is especially true for the legs, feet and digits of the feet.
U.S. Pat. No. 5,795,573 to Paradise discloses homeopathic topical pain relieving compositions for relieving pain due to injury or stress utilizing the combination of Arnica Montana, Rhus toxicodendron and Aesculus hippocastanum 
The article of Nicole Cryer entitled “Venom & Miracle Medicine?” in Science World, Nov. 1, 1997, p. 1 and 2 discloses the utility of venom-based drugs.
The Edward Dennis Group of the University of California has characterized the enzyme Phospholipase A2 from cobra venom as being involved in eicosanoid productions and phospholipids remodeling in cells involved with inflammation, parturition and neural function.